Multicenter Vitamin E Trial in Aging Persons With Down Syndrome

Overview

The purpose of this study is to determine the safety and effectiveness of 2,000 international units of Vitamin E (alpha tocopherol)on cognitive function of aging persons with Down syndrome. It is a randomized, double-blind, placebo-controlled trial lasting 36 months. It is expected that Vitamin E will slow the deterioration in cognitive functions associated with Alzheimer disease.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: April 2010

Detailed Description

Alzheimer disease (AD) continues to be the most serious health problem faced by aging persons with Down syndrome. AD is also a major public health concern in the aging general population. With increasing life expectancy there will be a dramatic increase in the prevalence of AD cases, which will pose a significant increased burden on the health care system and individual providers of care. Persons with Down syndrome are uniquely vulnerable to a form of Alzheimer disease indistinguishable from the sporadic variety that affects aging individuals from the general population. Oxidative damage is a highly plausible mechanism in the pathogenesis of this disease due to the overexpression of superoxide dismutase, associated with a gene located on chromosome 21, which is present in triplicate in the Down syndrome genotype. For the last six years, we have been conducting a clinical trial to determine the safety and efficacy of the anti-oxidant Vitamin E in slowing the cognitive and functional decline associated with the dementia of AD among individuals with DS. The study is a randomized, double-blind trial, stratified in a two-arm parallel design. The subjects are medically stable individuals who are 50 years of age or older at the time of screening. Among those randomized to the treatment arm, vitamin E is taken in the form of 1000 IU capsules for 36 months. Each subject is evaluated every 6 months for 3 years. The primary outcome is is the Brief Praxis Test (BPT), which is well-suited to quantifying cognitive decline in this population. The target enrollment of 350 persons is estimated to be sufficient to provide adequate statistical power to detect a slowing by one-third in the rate of cognitive decline with vitamin E treatment. The Data and Safety Monitoring Board (DSMB) for this trial includes 4 physicians, and a statistician with expertise in clinical trials. Each DSMB member receives a report on each serious adverse event (SAE) on a flow basis, and statistically summaries of unblinded safety data–including deaths, adverse events and vital signs–prior to each meeting of the DSMB. The most recent DSMB meeting took place on February 23,2010. The timeline for study completion is: recruitment of the study sample (N=350) was completed on 12/31/2008; the final 36-month evaluation will take place in 04/2010; statistical analysis and final report of results is expected to be completed by 12/31/2010.

Interventions

  • Drug: Alpha-Tocopherol
    • 1,000 International Units, two times a day for 36 months
  • Drug: Sugar Pill

Arms, Groups and Cohorts

  • Placebo Comparator: Sugar Pill
  • Active Comparator: Alpha-Tocopherol

Clinical Trial Outcome Measures

Primary Measures

  • The Brief Praxis Test
    • Time Frame: 36 months

Secondary Measures

  • The Fuld Object Memory Test
    • Time Frame: 36 Months
  • New Dot Test
    • Time Frame: 36 Months
  • Orientation Test
    • Time Frame: 36 Months
  • Vocabulary Test
    • Time Frame: 36 Months
  • Behavior and Function
    • Time Frame: 36 Months
  • Clinical Global Impression
    • Time Frame: 36 Months
  • Incident Dementia
    • Time Frame: 36 Months

Participating in This Clinical Trial

Inclusion Criteria

  • presence of clinically determined Down syndrome (karyotypes optional) – appropriately signed and witnessed consent form – age of 50 years or older at the start of the protocol – medically stable – medications stable more than 1 month – involvement/cooperation of informant/caregiver Exclusion Criteria:

  • medical/neurological condition (other than Alzheimer disease) associated with dementia – inability to adequately perform the Brief Praxis Test, as demonstrated by a score <20 – in the presence of dementia, modified Hachinski score > 4 at Screening Visit – major depression within 3 months – history of coagulopathy (inherited or acquired) – current use of anticoagulants – use of experimental medications within 2 months – regular use of vitamin E greater than 50 units per day during the previous 6 months – allergy to vitamin E

Gender Eligibility: All

Minimum Age: 50 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • New York State Institute for Basic Research
  • Collaborator
    • National Institute on Aging (NIA)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Arthur Dalton, Deputy Director – New York State Institute for Basic Research
  • Overall Official(s)
    • Paul S. Aisen, M.D., Study Director, University of California, San Diego
    • Mary C. Sano, Ph.D., Study Director, Bronx Veterans Medical Research Foundation
    • Howard F. Andrews, Ph.D., Study Director, New York Psychiatric Institute
    • Wei-Yann Tsai, Ph.D., Study Director, Columbia University

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.